FOXD2-AS1/miR-185-5p/CDC42 axis in chronic obstructive pulmonary disease: clinical significance and mechanistic insights

BACKGROUND: Long non-coding RNA (lncRNA), a key molecule within gene expression regulatory network, is important in various respiratory diseases. This study assessed the expression changes and regulatory mechanism of lncRNA FOXD2-AS1 in chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Two hundred COPD patients were enrolled, comprising 100 with AECOPD and 100 with stable COPD. 16HBE cells were exposed to cigarette smoke extract (CSE) to simulate disease conditions in vitro. Relative mRNA levels were measured via RT-qPCR. Cell function, including cell proliferation, apoptosis and inflammation, was assessed. Target binding genes were predicted using online tools, with their functions annotated via GO and KEGG analysis. RESULTS: Both stable COPD patients and AECOPD patients had significantly higher serum FOXD2-AS1 levels than healthy controls, with the highest values in AECOPD. It can differentiate stable COPD from healthy controls and AECOPD, and increased gradually with COPD stage progression. Silencing FOXD2-AS1 afforded protection against apoptotic and inflammatory phenotype induced by CSE in 16HBE cells. FOXD2-AS1 sponges miR-185-5p, which were downregulated in clinical serum samples and cell models. miR-185-5p downregulation reversed the effects of FOXD2-AS1 silencing on cell apoptosis and inflammation. CDC42, a downstream target of miR-185-5p, was upregulated in COPD patients and cell models, and negatively related to serum miR-185-5p levels. CDC42 reversed the role of FOXD2-AS1/ miR-185-5p in CSE-exposed 16HBE cells. CONCLUSIONS: Serum FOXD2-AS1 was markedly upregulated in COPD patients, with close correlation to disease severity. The FOXD2-AS1/miR-185-5p/CDC42 axis may contribute to COPD pathogenesis by mediating bronchial epithelial cell apoptosis and inflammation.